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• Liver fibrosis assessment by transient elastography in hepatitis C patients with normal ALT
  Ricardo Moreno-Otero
  Published on: 18 April 2016

• Published on: 18 April 2016

  Liver fibrosis assessment by transient elastography in hepatitis C patients with normal ALT

  • Ricardo Moreno-Otero, Gastroenterology and Hepatology Service.
  • Other Contributors:
    • Maria Trapero-Marugan and Jorge Mendoza

  Dear Editor,

  We read with interest the paper by Foucher et al.[1] where the authors assess the accuracy of transient elastography for the detection of cirrhosis. Its use to assessing the severity of chronic liver disease in other clinical scenarios warrant further evaluations. According to large population studies, the prevalence of chronically hepatitis C virus (HCV) infected patients who have persistently normal...

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  Dear Editor,

  We read with interest the paper by Foucher et al.[1] where the authors assess the accuracy of transient elastography for the detection of cirrhosis. Its use to assessing the severity of chronic liver disease in other clinical scenarios warrant further evaluations. According to large population studies, the prevalence of chronically hepatitis C virus (HCV) infected patients who have persistently normal serum aminotransferase (PN-ALT) levels is most likely around 30-50%.[2] A major problem is to define whether these patients may suffer a progressive disease; additionally, although no consensus exists regarding who must be treated and when antiviral therapy must be initiated, positive decisions have been reinforced by the recent results of a large clinical trial indicating that pegylated interferon plus ribavirin combination therapy is effective and safe in these patients with PN-ALT.[3] In a recent review the schedule of antiviral combination treatment of patients with chronic hepatitis C and normal aminotransferases is described and indication of antiviral therapy in some cases might be decided on the basis of histological findings[2]; hence, liver biopsy seems to be a key in this decision and a patient must be treated if there is significant fibrosis (>OR= F2). However, meanwhile liver biopsy remains the “gold standard” for the assessment of hepatic fibrosis, it represents an invasive procedure with some risks and limitations[1], and is not well accepted by all patients. Non-invasive methods such as Fibrotest, Forns’ index (FI) and APRI have been designed to assess liver fibrosis.[4] Fibroscan® (FS), a new transient elastography technique to measure liver stiffness or elasticity[5,6], have rised great expectancy as an alternative method for staging liver disease. Stiffness insignificantly correlates to fibrosis stage and is a promising, reproducible and independent of the operator, method for the detection of cirrhosis.[1,6] Our aim was the assessment by FS of hepatic fibrosis in patients infected by HCV and PN-ALT, comparing the accuracy of FS to that previously described for biomarkers.

  We analysed prospectively 28 chronically HCV infected patients (18 females) with PN-ALT (at least three determinations yearly), assessing hepatic fibrosis by FS. Concordances and correlations between FS and FI and APRI were also evaluated. Almost all consecutive patients were asymptomatic and none of them have had the well known complications of advanced liver disease or cirrhosis.[7] Patients’ characteristics (mean ± SD) were as follow: age 44.3 ± 10 years, BMI 24.1± 2.8 Kg/m2, platelets count 249.6 ± 58 /mm3, serum cholesterol levels 190.5 ± 26 mg/dL, serum AST levels 25 ± 5 IU/L, serum ALT levels 27.7 ± 6.7 IU/L and serum GGT levels 23.2 ± 21 IU/L. Results of the study were as follow: 26 (92.8%) patients had HCV-genotype 1. Mean value of FS was 6.35 ± 3.3 KPa, indicating absence or mild stage of fibrosis (<8.5 KPa); as expected, mean values of FI (3.35 ± 1.4) and APRI (0.27 ± 0.09) also reflects minimal or no fibrosis (<4.5 and <0.5, respectively). These provocative findings show that this cohort of PN-ALT chronically HCV infected patients have a low stage of fibrosis according to three non- invasive methods. A previous study has compared and validated these methods in chronic hepatitis C patients with elevated ALT.[8]

  Liver biopsy has been used as the “gold standard” for the assessment of hepatic fibrosis. It has been used for staging the liver damage in chronic viral hepatitis and for decision analysis as to the need of treatment in patients with chronic hepatitis C. The limitations of biopsy such as patient acceptability, sampling error or diagnostic inaccuracy, and the remote risk of complications, have led clinical investigators to study alternative methods to stage chronic viral hepatitis.[1,4,9] Serum biological markers determination is the most widely used procedure for stimation of liver fibrosis[9]; combining serum biomarkers with FS may increase the accuracy of these non-invasive methods, suggesting that it may be valid to circumvent the limitations of hepatic histology.[8,9] FS is an objective and safe technique, enthusiastically accepted by patients. Hence, periodical examinations can be performed as a follow-up protocol for assessment of hepatic fibrosis progression or improvement. Moreover, it is a precise method for the detection of cirrhosis and promising in order to predict complications of cirrhosis.[1] Accordingly, our data may suggest that therapeutic management of PN-ALT patients could be established according to fibrosis stage detected along successive FS examinations. Those PN-ALT patients with evidence of fibrosis by FS would need to start an early antiviral treatment. Although with the inconvenience of less effectivity in obese subjects, transient elastography may be very helpful in a better diagnostic and therapeutic management of PN-ALT chronically HCV infected patients, questioning the leading role of biopsy.[8,9] Further studies on this topic may be warranted in order to evaluate the diagnostic accuracy for staging hepatic fibrosis, the natural history of disease and the optimised response to combination antiviral therapy. Additionally, it has been demonstrated that combining a FS measurement with biomarkers may increase the diagnostic accuracy of both tests.[8,9] In conclusion, repeated stiffness assessment appears to be a good and safe alternative method to indicate antiviral combination therapy in PN-ALT patients reluctant to liver biopsy. (Grant ISC III 03/02).

  References

  1. Foucher J, Chanteloup E, Vergniol J, et al. Diagnosis of cirrhosis by transient elastography (Fibroscan®): a prospective study. Gut online 14 Jul 2005.

  2. Alberti A. Towards more individualised management of hepatitis C virus patients with initially or persistently normal alanineaminotransferase levels. J Hepatol 2005;42:266-74.

  3. Zeuzem S, Diago M, Gane E, et al. Peginterferon alfa-2a (40 kilodaltons) and ribavirin in patients with chronic hepatitis C and normal aminotransferase levels. Gastroenterology 2004;127:1724-32.

  4. Wai CT, Greenson JK, Fontana RJ, et al. A simple non-invasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology 2003; 38:518-26.

  5. Sandrin L, Fourquet B, Hasquenoph JM, et al. Transient elastography : a new noninvasive method for assessment of hepatic fibrosis. Ultrasound Med Biol 2003; 29:1705-13.

  6. Ziol M, Handra-Luca A, Kettaneh A, et al. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. Hepatology 2005;41:48-54.

  7. Benvegnù L, Gios M, Bocato S et al. Natural history of compensated viral cirrhosis: a prospective study on the incidence and hierarchy of major complications. Gut 2004; 53:744-9.

  8. Castera L, Vergniol J, Foucher J, et al. Prospective comparison of transient elastography, fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology 2005; 128: 343-50.

  9. Afdhal NH, Nunes D. Evaluation of liver fibrosis: a concise review. Am J Gastroenterol 2004;99:1160-74.

  Maria Trapero-Marugan, Jorge Mendoza and Ricardo Moreno-Otero.

  Gastroenterology and Hepatology Service (ISC III 03/02)
  Hospital Universitario de La Princesa
  Autonomous University of Madrid
  Spain

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  Conflict of Interest:
  None declared.

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